Objective: This study examines the relationship between childhood abuse and neglect and sexual risk behavior in middle adulthood and whether psychosocial factors (risky romantic relationships, affective symptoms, drug and alcohol use, and delinquent and criminal behavior) mediate this relationship. Method: Children with documented cases of physical abuse, sexual abuse, and neglect (ages 0-11) processed during 1967-1971 were matched with nonmaltreated children and followed into middle adulthood (approximate age 41). Mediators were assessed in young adulthood (approximate age 29) through in-person interviews between 1989 and 1995 and official arrest records through 1994 (N = 1,196). Past year HIV-risk sexual behavior was assessed via self-reports during 2003-2004 (N = 800). Logistic regression was used to examine differences in sexual risk behavior between the abuse and neglect and control groups, and latent variable structural equation modeling was used to test mediator models. Results: Child abuse and neglect was associated with increased likelihood of risky sexual behavior in middle adulthood, odds ratio = 2.84, 95% CI [1.74, 4.64], p less than or equal to 0.001, and this relationship was mediated by risky romantic relationships in young adulthood. Conclusions: Results of this study draw attention to the potential long-term consequences of child abuse and neglect for physical health, in particular sexual risk, and point to romantic relationships as an important focus of intervention and prevention efforts. (Contains 3 figures and 3 tables.)